Nitric oxide in neurodegeneration: potential benefits of non-steroidal anti-inflammatories

Doherty, Gayle H.

doi:10.1007/s12264-011-1530-6

Cited by 82 publications

(60 citation statements)

References 131 publications

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“…NO is released from activated microglia, and neurons are remarkably sensitive to NO-induced cell death [2]. High levels of NO produced by iNOS from activated microglial cells are associated with the progression of various neurodegenerative diseases [8]. ROS are also strongly associated with microglial neuroinflammatory processes in neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

Gardenia jasminoides Exerts Anti-inflammatory Activity via Akt and p38-dependent Heme Oxygenase-1 Upregulation in Microglial Cells

Song¹,

Shin²,

Kim³

et al. 2017

Journal of Life Science

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Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.

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Section: Discussionmentioning

confidence: 99%

Gardenia jasminoides Exerts Anti-inflammatory Activity via Akt and p38-dependent Heme Oxygenase-1 Upregulation in Microglial Cells

Song¹,

Shin²,

Kim³

et al. 2017

Journal of Life Science

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“…In vitro studies demonstrated that medium from M1 macrophages is toxic to cortical neurons [51][52][53] . NO, glutamine and reactive oxygen species produced by M1 macrophages or microglia are generally accepted to lead to neuronal degeneration in MS [54][55][56] . Sodium channel blockade can rescue axons from NO-mediated degeneration in EAE [57,58] .…”

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confidence: 99%

Polarization of macrophages and microglia in inflammatory demyelination

Cao

2013

Neurosci. Bull.

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Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system, and microglia and macrophages play important roles in its pathogenesis. The activation of microglia and macrophages accompanies disease development, whereas depletion of these cells significantly decreases disease severity. Microglia and macrophages usually have diverse and plastic phenotypes. Both pro-inflammatory and antiinflammatory microglia and macrophages exist in MS and its animal model, experimental autoimmune encephalomyelitis. The polarization of microglia and macrophages may underlie the differing functional properties that have been reported. in this review, we discuss the responses and polarization of microglia and macrophages in MS, and their effects on its pathogenesis and repair. Harnessing their beneficial effects by modulating their polarization states holds great promise for the treatment of inflammatory demyelinating diseases.Keywords: macrophage; microglia; polarization; demyelination; remyelination IntroductionMultiple sclerosis (MS) is a chronic autoimmune inflammatory and demyelinating disease characterized by inflammation, demyelination, axonal damage, gliosis and destruction of the blood-brain barrier [1][2][3] . Although the T-helper (Th) cells Th-1 and Th-17 were thought to be the main response effectors for autoimmune inflammation, macrophages and microglia do play an important role in the pathogenesis of MS. The pathology of newly-forming lesions in relapsingremitting MS shows only microglial activation and macrophage infiltration in demyelinating areas, with rare lymphocyte infiltration [4,5] . Moreover, macrophage depletion and microglial paralysis significantly suppress the progress of experimental autoimmune encephalomyelitis (EAE), the animal model of MS [6,7] .Macrophages and microglia play important roles in bridging the innate and adaptive immune reponses. Under normal physiological conditions, macrophages monitor the tissue environment for pathogens, maintain tissue homeostasis, phagocytose dead and dying cells, and respond rapidly to perturbations in the local environment. Microglia share many phenotypic and functional characteristics with macrophages. in the adult central nervous system (CNS), microglia are on constant surveillance for perturbations resulting from injury or disease [8] . In MS, in which pro-inflammatory, neurotoxic and myelin-attacking microglia and macrophages predominate, some microglia and macrophages with anti-inflammatory, neuroprotective and remyelinationpromoting properties are also present [9] . These conflicting lines of evidence have led to confusion and considerable debate regarding the harmful versus the beneficial roles of macrophages and microglia in MS.The polarization of macrophages and microglia may underlie their differing functional properties. Taking advantage of their beneficial effects by modulating their polarization states holds great promise for the treatment of CNS demyelinating diseases [10][11][12][13] . in this review, we discuss the ...

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“…24) In this context, compounds that can modulate the neuroinflammatory processes may prove useful in the control of neurodegeneration. 2,23) Both 4-methylcoumarin compounds investigated in this study were able to exert anti-inflammatory effects in primary rat microglial cultures, evidenced by inhibition of proinflammatory and neurotoxic mediators NO, PGE 2 , TXB 2 and TNF-α production and also by lowering iNOS and COX-2 protein expression, but without any significant effect on COX-1 and COX-2 enzyme activities in whole blood assay.…”

Section: Discussionmentioning

confidence: 87%

“…3,4,23) Microglia, which are the main cellular components of the brain immune system, play an important role in the process of inflammation in the CNS 3) and their chronic activation may contribute to the development and progression of neurodegenerative diseases. 24) In this context, compounds that can modulate the neuroinflammatory processes may prove useful in the control of neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

“…23,26) 4-Methylcoumarin derivatives bearing 7,8-dihydroxy and 7,8-diacetoxy moieties have been reported to be potent antioxidant compounds. [12][13][14] Most of these reports have suggested that 7,8-dihydroxy confers higher activity compared to 7,8-diacetoxy, 13,14) probably due the important contribution of catechol moiety to the antioxidant activity.…”

Section: Discussionmentioning

confidence: 99%

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4-Methylcoumarin Derivatives with Anti-inflammatory Effects in Activated Microglial Cells

Togna

Firuzi

Latina

et al. 2014

Biological & Pharmaceutical Bulletin

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Inflammation contributes to the pathogenesis of neurodegenerative diseases and anti-inflammatory compounds may have a role in prevention or treatment of these pathologies. 4-Methylcoumarins are effective antioxidants with anti-inflammatory properties. In this study, the inhibitory effects of two 4-methylcoumarin derivatives, 7,8-dihydroxy-3-ethoxycarbonylmethyl-4-methylcoumarin (DHEMC) and 7,8-diacetoxy-3-ethoxycarbonylmethyl-4-methylcoumarin (DAEMC) were examined on the inflammatory processes induced by lipopolysaccharide (LPS) in activated primary rat microglial cultures. LPS-induced production of nitric oxide (NO, measured by Griess method) and other pro-inflammatory mediators, thromboxane (TX) B 2 and prostaglandin (PG) E 2 (both determined by radioimmunoassay (RIA)), as well as tumor necrosis factor (TNF)-α (determined by enzyme-linked immunosorbent assay (ELISA)) were inhibited in the presence of 100 µM DHEMC and DAEMC. DAEMC was able to significantly inhibit NO, TXB 2 and TNF-α production also at 50 µM. Both compounds at 100 µM significantly lowered cyclooxygenase-2 (COX-2) protein expression in LPS-stimulated microglial cells measured by Western blot, but only DAEMC showed an inhibitory effect on inducible nitric oxide synthase (iNOS) protein expression at 100 µM. In conclusion, our findings show that 4-methylcoumarin derivatives can modulate inflammatory pathways in microglial cells, probably by acting at the protein expression level.

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Nitric oxide in neurodegeneration: potential benefits of non-steroidal anti-inflammatories

Cited by 82 publications

References 131 publications

Gardenia jasminoides Exerts Anti-inflammatory Activity via Akt and p38-dependent Heme Oxygenase-1 Upregulation in Microglial Cells

Gardenia jasminoides Exerts Anti-inflammatory Activity via Akt and p38-dependent Heme Oxygenase-1 Upregulation in Microglial Cells

Polarization of macrophages and microglia in inflammatory demyelination

4-Methylcoumarin Derivatives with Anti-inflammatory Effects in Activated Microglial Cells

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